دورية أكاديمية
Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels.
العنوان: | Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels. |
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المؤلفون: | Xiao-Fei Gao, Jin-Jing Yao, Yan-Lin He, Changlong Hu, Yan-Ai Mei |
المصدر: | PLoS ONE, Vol 7, Iss 11, p e49384 (2012) |
بيانات النشر: | Public Library of Science (PLoS), 2012. |
سنة النشر: | 2012 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | (+)-SKF 10047 (N-allyl-normetazocine) is a prototypic and specific sigma-1 receptor agonist that has been used extensively to study the function of sigma-1 receptors. (+)-SKF 10047 inhibits K(+), Na(+) and Ca2+ channels via sigma-1 receptor activation. We found that (+)-SKF 10047 inhibited Na(V)1.2 and Na(V)1.4 channels independently of sigma-1 receptor activation. (+)-SKF 10047 equally inhibited Na(V)1.2/1.4 channel currents in HEK293T cells with abundant sigma-1 receptor expression and in COS-7 cells, which barely express sigma-1 receptors. The sigma-1 receptor antagonists BD 1063,BD 1047 and NE-100 did not block the inhibitory effects of (+)-SKF-10047. Blocking of the PKA, PKC and G-protein pathways did not affect (+)-SKF 10047 inhibition of Na(V)1.2 channel currents. The sigma-1 receptor agonists Dextromethorphan (DM) and 1,3-di-o-tolyl-guanidine (DTG) also inhibited Na(V)1.2 currents through a sigma-1 receptor-independent pathway. The (+)-SKF 10047 inhibition of Na(V)1.2 currents was use- and frequency-dependent. Point mutations demonstrated the importance of Phe(1764) and Tyr(1771) in the IV-segment 6 domain of the Na(V)1.2 channel and Phe(1579) in the Na(V)1.4 channel for (+)-SKF 10047 inhibition. In conclusion, our results suggest that sigma-1 receptor agonists directly inhibit Na(V)1.2/1.4 channels and that these interactions should be given special attention for future sigma-1 receptor function studies. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 |
Relation: | http://europepmc.org/articles/PMC3489664?pdf=render; https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0049384 |
URL الوصول: | https://doaj.org/article/0b4c76f935d04c589a2363160d71ad86 |
رقم الأكسشن: | edsdoj.0b4c76f935d04c589a2363160d71ad86 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 |
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DOI: | 10.1371/journal.pone.0049384 |